Today, a wide variety of chemotherapeutic agents are used for treatment, and suppression of tumors, especially malignant solid tumors. Although these agents may have a tumor reducing effect, it is often not possible for these known agents to effect a cure due to acquisition of resistance against the agent by the cancer, relapse of the tumors, and so on. Therefore, further superior antitumor agents are needed.
While stilbene derivatives, having cis-stilbene as a fundamental skeleton, are known to exhibit strong mitosis inhibitory activities and cytotoxity, most stilbene derivatives are not yet available as pharmaceutical agents because of their low solubility in water.
Recently, it has been discovered that certain stilbene derivatives having activity for inhibiting tubulin polymerization also have improved water solubility. These include the phosphorylated pro-drug of combretastatin-A4 (See U.S. Pat. No. 5,561,122), and the stilbene derivatives disclosed in U.S. Pat. No. 5,674,906. The clinical use of these stilbene derivatives is felt to be promising. However, more work is needed to improve the efficacy of these and other stilbene derivatives.
It is an object of the present invention to develop a superior antitumor agent, specifically, to develop a pharmaceutical preparation capable of improving the efficacy of a stilbene derivative and, in particular, to develop and provide antitumor agents exhibiting superior safety and efficacy in treating malignant tumors.